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Biotech / Medical : XOMA. Bull or Bear? -- Ignore unavailable to you. Want to Upgrade?


To: Andrew H who wrote (4247)10/23/1997 7:28:00 AM
From: Robert K.  Respond to of 17367
 
You beat me on that post Andy, here is my follow-up to it.
Peptides from Bactericidal/Permeability-Increasing Protein (BPI) are Cytotoxic for Mycoplasma and L-Forms of Gram-Positive Bacteria

Arnold H. Horwitz*, Roger Little**, Mitch Fadem** and Rossana E. Nadell*.
*XOMA Corporation, Santa Monica, CA 90404; and **Berkeley, CA 94710.

Synthetic peptides comprising amino acids 85-99 (Domain II) and 148-161 (DomainöIII) of BPI are bactericidal for gram-negative bacteria. The Domain III peptide is also bactericidal at high concentrations against a strain of the gram-positive bacterium, Staphylococcus aureus. In this study, we have used a sensitive radial diffusion assay with ~ 5 x 105öcells/ml to examine the bactericidal activities of these Domain II and III peptides, a Domain I peptide (21-50) and one consisting of Domains II and III (II/III) against bacterial forms (containing a cell wall) and L-forms (lacking a cell wall) of S. aureus, Streptococcus pneumoniae and Streptococcus pyogenes and the mycoplasma, Acholeplasma laidlawii, a naturally-occurring cell wall-less prokaryote.


The bacterial form of the S. aureus strain used in these experiments was insensitive to all of the tested peptides while the bacterial forms of S. pneumoniae and S.öpyogenes were slightly sensitive to the Domain III and II/III peptides, but not to the Domain I and II peptides. By comparison, all but the Domain I peptide were bactericidal for L-forms of the above bacteria, although the Domain II peptide was only slightly active and only the Domain III and II/III peptides were effective against the Acholeplasma. The relative potency against the L-forms was Domain II/III > Domain III > Domain II.


The peptides were generally more bactericidal for the Acholeplasma and L-forms than for the most sensitive bacterial forms, generating ~ 75-300 mm2 versus ~ 20-75 mm2 inhibition zones, respectively, for the most potent peptides tested at their highest concentrations in the radial diffusion assay. This activity was similar to that observed with these peptides on a sensitive gram-negative bacterium, E. coli J5, tested under the same conditions. These results suggest that BPI-derived peptides may be effective in treating mycoplasma and gram-positive bacteria, particularly in conjunction with antibiotics that target and remove the cell wall.

c Copyright 1996, XOMA Corporation



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